Risperidone is a new antipsychotic agent recently approved for the treatment of schizophrenia. It has demonstrated superior efficacy to haloperidol for positive and negative symptoms and is associated with low levels of extrapyramidal symptoms. Clozapine is the only other antipsychotic drug that has demonstrated superior efficacy compared to conventional neuroleptics, and it too is associated with low levels of extrapyramidal symptoms. Preclinical studies indicate risperidone has a unique biochemical profile in that it is more highly potent at the dopamine D-2 and serotonin 5HT-2 receptors than clozapine. The purpose of this study is to compare risperidone's neurochemical properties with those of the atypical neuroleptic clozapine. In addition, the relationship between risperidone's biochemical effects and clinical efficacy will be examined. The biochemical variables are D-2 occupancy as determined by IBZM/SPECT and CSF and plasma metabolite levels. To date, 35 patients with schizophrenia or schizoaffective disorder have entered the double-blind study and we will analyze the symptom and neurochemical data in the upcoming year. Some of the SPECT/IBZM data are published (Pickar et al, 1996) and the remaining data are being analyzed currently.